Paclitaxel (Taxol®) is a natural product that can be isolated from the bark of the yew tree Taxus brevifolia. Paclitaxel has become an effective treatment for various types of cancers, such as ovarian, breast, and lung. Taxol® has the biological activity of binding the protein β-tubulin and stabilizing microtubules in the cytosol. Additionally, paclitaxel inhibits microtubule polymerization dynamics and can trigger cellular death via apoptosis. Although paclitaxel is widely used as a therapeutic, some mechanisms underlying its selective cytotoxicity towards cancer cells remain unknown. Paclitaxel and related compounds, such as taxanes and taxoids, can exhibit antimitotic activity against rapidly dividing cancer cell lines and xenografts that double every 1-12 days, suggesting that effects against rapidly proliferating cells might provide selectivity against tumors in human patients. However, these types of compounds also show major effects against slow growing tumors (median doubling time of ˜147 days) in patients, while sparing rapidly proliferating normal cells in bone marrow, gut, and other tissues.

Fluorescent analogues of paclitaxel have been used for studying their anticancer effects. An example of such a compound termed Flutax-2® includes paclitaxel linked at the 7-position through a β-Ala ester to the fluorophore Oregon Green (OG), as shown below. The term Flutax-2® has also been used to describe a related fluorescent probe where paclitaxel is linked to OG via an L-Ala ester (termed here Flutax-2® (L-Ala)). The side-chain of Taxol® has also been linked to the BODIPY fluorophore, but these probes are generally not considered suitable for imaging of living cells.

At physiological pH, OG exists as a highly polar dianion. In Flutax-2, this increases the polarity of paclitaxel by almost 1000-fold, which alters its calculated octanol-water distribution/partition coefficient from c Log DpH7.4=2.9 (paclitaxel) to c Log DpH7.4=0.0 (Flutax-2®). Given that most small molecule drugs are generally moderately hydrophobic (c Log DpH7.4˜2), which facilitates passive diffusion across membranes, Flutax-2® differs substantially from paclitaxel under physiological conditions.
Therefore, it may be advantageous to provide more paclitaxel-like fluorescent probes.